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Identification of cell-type-specific mutations in nodal T-cell lymphomas

Nguyen, T B, Sakata-Yanagimoto, M, Asabe, Y, Matsubara, D, Kano, J, Yoshida, K, Shiraishi, Y, Chiba, K, Tanaka, H, Miyano, S, Izutsu, K, Nakamura, N, Takeuchi, K, Miyoshi, H, Ohshima, K, Minowa, T, Ogawa, S, Noguchi, M, Chiba, S·2017·Blood Cancer Journal
DOI 10.1038/bcj.2016.122PMC PMC5301031
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Abstract

Recent genetic analysis has identified frequent mutations in ten-eleven translocation 2 (TET2), DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 2 (IDH2) and ras homolog family member A (RHOA) in nodal T-cell lymphomas, including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified. We examined the distribution of mutations in these subtypes of mature T-/natural killer cell neoplasms to determine their clonal architecture. Targeted sequencing was performed for 71 genes in tumor-derived DNA of 87 cases. The mutations were then analyzed in a programmed death-1 (PD1)-positive population enriched with tumor cells and CD20-positive B cells purified by laser microdissection from 19 cases. TET2 and DNMT3A mutations were identified in both the PD1+ cells and the CD20+ cells in 15/16 and 4/7 cases, respectively. All the RHOA and IDH2 mutations were confined to the PD1+ cells, indicating that some, including RHOA and IDH2 mutations, being specific events in tumor cells. Notably, we found that all NOTCH1 mutations were detected only in the CD20+ cells. In conclusion, we identified both B- as well as T-cell-specific mutations, and mutations common to both T and B cells. These findings indicate the expansion of a clone after multistep and multilineal acquisition of gene mutations.

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Figures

Figure 1 Targeted sequencing result of 87 nodal T-cell lymphoma samples. TET2-, RHOA-, IDH2- and DNMT3A-mutated cases are indicated by blue, red, orange and green boxes, respectively. Other recurrently mutated genes are in purple. The laser-microdissected samples are indicated in red letters.
Figure 1 Targeted sequencing result of 87 nodal T-cell lymphoma samples. TET2-, RHOA-, IDH2- and DNMT3A-mutated cases are indicated by blue, red, orange and green boxes, respectively. Other recurrently mutated genes are in purple. The laser-microdissected samples are indicated in red letters.CC BY · PubMed Central
Figure 2 RHOA mutations are specific to PD1+ cells. (a) An example of the immunostaining pattern for PD1 and CD20 in AITL. Left, PD1+ cells; right, CD20+ cells. (b) Sequences of G17V RHOA mutations in whole tumor, PD1+ cells and CD20+ cells. The numeric values indicate allele frequencies of mutations defined by amplicon-based deep sequencing. The AITL samples are indicated in black letters. The nodal PTCL with TFH phenotype sample is indicated in red letters *: RHOA c.A51T:p.G17V, silent mutation. The filled and dashed red arrows indicate mutations and no mutations, respectively.
Figure 2 RHOA mutations are specific to PD1+ cells. (a) An example of the immunostaining pattern for PD1 and CD20 in AITL. Left, PD1+ cells; right, CD20+ cells. (b) Sequences of G17V RHOA mutations in whole tumor, PD1+ cells and CD20+ cells. The numeric values indicate allele frequencies of mutations defined by amplicon-based deep sequencing. The AITL samples are indicated in black letters. The nodal PTCL with TFH phenotype sample is indicated in red letters *: RHOA c.A51T:p.G17V, silent mutation. The filled and dashed red arrows indicate mutations and no mutations, respectively.CC BY · PubMed Central
Figure 3 Distributions of TET2/DNMT3A/RHOA/IDH2/NOTCH1 mutations and IgH VDJ status. Allele frequencies of TET2/DNMT3A/RHOA/IDH2/NOTCH1 mutations in whole tumor, PD1+ cells and CD20+ cells are shown. The blue boxes represent positive TET2 mutations; the green boxes, positive DNMT3A mutations; the red boxes, positive RHOA mutations; the orange boxes, positive IDH2 mutations; the purple boxes, positive NOTCH1 mutations; the yellow boxes, no mutations; and the white boxes, not examined. The numeric values indicate allele frequencies of mutations defined by deep sequencing, except for that in the box surrounded by bold red lines which was estimated by Sanger sequencing. IgH VDJ status indicates the IgH VDJ rearrangement status in whole-tumor-derived DNA. The AITL samples are indicated in black letters. The nodal PTCL with TFH phenotype sample is indicated in red letters. The PTCL-NOS/nodal PTCL with TFH phenotype sample is indicated in blue letters. MC, monoclonality; OC, oligoclonality; Pos: positivity was evaluated only by Sanger sequencing. Multiple TET2 mutations were identified in PTLC2, 8, 60, 63, 77, 136, 121, 123, 127 and 129.
Figure 3 Distributions of TET2/DNMT3A/RHOA/IDH2/NOTCH1 mutations and IgH VDJ status. Allele frequencies of TET2/DNMT3A/RHOA/IDH2/NOTCH1 mutations in whole tumor, PD1+ cells and CD20+ cells are shown. The blue boxes represent positive TET2 mutations; the green boxes, positive DNMT3A mutations; the red boxes, positive RHOA mutations; the orange boxes, positive IDH2 mutations; the purple boxes, positive NOTCH1 mutations; the yellow boxes, no mutations; and the white boxes, not examined. The numeric values indicate allele frequencies of mutations defined by deep sequencing, except for that in the box surrounded by bold red lines which was estimated by Sanger sequencing. IgH VDJ status indicates the IgH VDJ rearrangement status in whole-tumor-derived DNA. The AITL samples are indicated in black letters. The nodal PTCL with TFH phenotype sample is indicated in red letters. The PTCL-NOS/nodal PTCL with TFH phenotype sample is indicated in blue letters. MC, monoclonality; OC, oligoclonality; Pos: positivity was evaluated only by Sanger sequencing. Multiple TET2 mutations were identified in PTLC2, 8, 60, 63, 77, 136, 121, 123, 127 and 129.CC BY · PubMed Central
Figure 4 Distribution of newly identified gene mutations in nodal T-cell lymphomas. The results of Sanger sequencing and/or amplicon-based deep sequencing for some newly identified gene mutations in whole tumor, PD1+ cells and CD20+ cells are shown. The numeric values indicate allele frequencies of mutations defined by deep sequencing. The AITL samples are indicated in black letters. The PTCL-NOS/nodal PTCL with TFH phenotype sample is indicated in blue letters. NA, not analyzed by deep sequencing. The filled and dashed red arrows indicate mutations and no mutations, respectively.
Figure 4 Distribution of newly identified gene mutations in nodal T-cell lymphomas. The results of Sanger sequencing and/or amplicon-based deep sequencing for some newly identified gene mutations in whole tumor, PD1+ cells and CD20+ cells are shown. The numeric values indicate allele frequencies of mutations defined by deep sequencing. The AITL samples are indicated in black letters. The PTCL-NOS/nodal PTCL with TFH phenotype sample is indicated in blue letters. NA, not analyzed by deep sequencing. The filled and dashed red arrows indicate mutations and no mutations, respectively.CC BY · PubMed Central
Figure 5 B-cell-specific mutations in nodal T-cell lymphomas. The results of Sanger sequencing and/or amplicon-based deep sequencing for some newly identified gene mutations in whole tumor, PD1+ cells and CD20+ cells are shown. The numeric values indicate allele frequencies of mutations defined by deep sequencing. The AITL samples are indicated in black letters. The PTCL-NOS/nodal PTCL with TFH phenotype sample is indicated in blue letters. NA, not analyzed by deep sequencing. The filled and dashed red arrows indicate mutations and no mutations, respectively. NOTCH1 is marked by red letters because this is repetitive.
Figure 5 B-cell-specific mutations in nodal T-cell lymphomas. The results of Sanger sequencing and/or amplicon-based deep sequencing for some newly identified gene mutations in whole tumor, PD1+ cells and CD20+ cells are shown. The numeric values indicate allele frequencies of mutations defined by deep sequencing. The AITL samples are indicated in black letters. The PTCL-NOS/nodal PTCL with TFH phenotype sample is indicated in blue letters. NA, not analyzed by deep sequencing. The filled and dashed red arrows indicate mutations and no mutations, respectively. NOTCH1 is marked by red letters because this is repetitive.CC BY · PubMed Central

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Research works printed but not linked: 45

  1. Wang SS, Vose MJ . Epidemiology and Prognosis of T-cell Lymphoma. Humana Press, 2013, pp 25–38. · DOI
  2. Park S, Ko YH . Peripheral T cell lymphoma in Asia. Int J Hematol 2014; 99: 227–239. · DOI
  3. Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM et al. Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr 2014; 2014: 66–75. · DOI
  4. de Leval L, Gaulard P . Pathobiology and molecular profiling of peripheral T-cell lymphomas. Hematology Am Soc Hematol Educ Program 2008, 272–279. · DOI
  5. Rodriguez-Pinilla SM, Atienza L, Murillo C, Perez-Rodriguez A, Montes-Moreno S, Roncador G et al. Peripheral T-cell lymphoma with follicular T-cell markers. Am J Surg Pathol 2008; 32: 1787–1799. · DOI
  6. Lemonnier F, Couronne L, Parrens M, Jais JP, Travert M, Lamant L et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood 2012; 120: 1466–1469. · DOI · Paper page
  7. Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet 2014; 46: 171–175. · DOI
  8. Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet 2014; 46: 166–170. · DOI
  9. Odejide O, Weigert O, Lane AA, Toscano D, Lunning MA, Kopp N et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood 2014; 123: 1293–1296. · DOI · Paper page
  10. Yang L, Rau R, Goodell MA . DNMT3A in haematological malignancies. Nat Rev Cancer 2015; 15: 152–165. · DOI
  11. Cairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L, Jais JP et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood 2012; 119: 1901–1903. · DOI
  12. Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet 2014; 46: 371–375. · DOI
  13. Quivoron C, Couronne L, Della Valle V, Lopez CK, Plo I, Wagner-Ballon O et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 2011; 20: 25–38. · DOI · Paper page
  14. Nguyen TB, Sakata-Yanagimoto M, Nakamoto-Matsubara R, Enami T, Ito Y, Kobayashi T et al. Double somatic mosaic mutations in TET2 and DNMT3A--origin of peripheral T cell lymphoma in a case. Ann Hematol 2015; 94: 1221–1223. · DOI
  15. Couronne L, Bastard C, Bernard OA . TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med 2012; 366: 95–96. · DOI · Paper page
  16. Kopan R, Ilagan MX . The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 2009; 137: 216–233. · DOI
  17. Weng AP, Ferrando AA, Lee W, Morris JPt, Silverman LB, Sanchez-Irizarry C et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004; 306: 269–271. · DOI
  18. Pancewicz J, Taylor JM, Datta A, Baydoun HH, Waldmann TA, Hermine O et al. Notch signaling contributes to proliferation and tumor formation of human T-cell leukemia virus type 1-associated adult T-cell leukemia. Proc Natl Acad Sci USA 2010; 107: 16619–16624. · DOI
  19. Puente XS, Pinyol M, Quesada V, Conde L, Ordonez GR, Villamor N et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011; 475: 101–105. · DOI
  20. Kridel R, Meissner B, Rogic S, Boyle M, Telenius A, Woolcock B et al. Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma. Blood 2012; 119: 1963–1971. · DOI
  21. Wang K, Li M, Hakonarson H . ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010; 38: e164. · DOI
  22. Chang X, Wang K . wANNOVAR: annotating genetic variants for personal genomes via the web. J Med Genet 2012; 49: 433–436. · DOI
  23. van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003; 17: 2257–2317. · DOI
  24. Kikushige Y, Ishikawa F, Miyamoto T, Shima T, Urata S, Yoshimoto G et al. Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia. Cancer Cell 2011; 20: 246–259. · DOI
  25. McKenney AS, Levine RL . Isocitrate dehydrogenase mutations in leukemia. J Clin Invest 2013; 123: 3672–3677. · DOI
  26. Wang C, McKeithan TW, Gong Q, Zhang W, Bouska A, Rosenwald A et al. IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma. Blood 2015; 126: 1741–1752. · DOI
  27. Chiba S . Guest editorial: preleukemia/prelymphoma-what is old, what is new? Int J Hematol 2015; 102: 511–512. · DOI
  28. Shlush LI, Zandi S, Itzkovitz S, Schuh AC . Aging, clonal hematopoiesis and preleukemia: not just bad luck? Int J Hematol 2015; 102: 513–522. · DOI
  29. Damm F, Mylonas E, Cosson A, Yoshida K, Della Valle V, Mouly E et al. Acquired initiating mutations in early hematopoietic cells of CLL patients. Cancer Discov 2014; 4: 1088–1101. · DOI
  30. Kikushige Y, Miyamoto T . Hematopoietic stem cell aging and chronic lymphocytic leukemia pathogenesis. Int J Hematol 2014; 100: 335–340. · DOI
  31. Busque L, Patel JP, Figueroa ME, Vasanthakumar A, Provost S, Hamilou Z et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet 2012; 44: 1179–1181. · DOI · Paper page
  32. Xie M, Lu C, Wang J, McLellan MD . Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 2014; 20: 1472–1478. · DOI · Paper page
  33. Bruggemann M, White H, Gaulard P, Garcia-Sanz R, Gameiro P, Oeschger S et al. Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies. Report of the BIOMED-2 Concerted Action BHM4 CT98-3936. Leukemia 2007; 21: 215–221. · DOI
  34. Higgins JP, van de Rijn M, Jones CD, Zehnder JL, Warnke RA . Peripheral T-cell lymphoma complicated by a proliferation of large B cells. Am J Clin Pathol 2000; 114: 236–247. · DOI
  35. Tan BT, Warnke RA, Arber DA . The frequency of B- and T-cell gene rearrangements and epstein-barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations. J Mol Diagn 2006; 8: 466–475, quiz 527. · DOI
  36. Zettl A, Lee SS, Rudiger T, Starostik P, Marino M, Kirchner T et al. Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angloimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Am J Clin Pathol 2002; 117: 368–379. · DOI
  37. Hawley RC, Cankovic M, Zarbo RJ . Angioimmunoblastic T-cell lymphoma with supervening Epstein-Barr virus-associated large B-cell lymphoma. Arch Pathol Lab Med 2006; 130: 1707–1711. · DOI
  38. Willenbrock K, Brauninger A, Hansmann ML . Frequent occurrence of B-cell lymphomas in angioimmunoblastic T-cell lymphoma and proliferation of Epstein-Barr virus-infected cells in early cases. Br J Haematol 2007; 138: 733–739. · DOI
  39. Attygalle AD, Kyriakou C, Dupuis J, Grogg KL, Diss TC, Wotherspoon AC et al. Histologic evolution of angioimmunoblastic T-cell lymphoma in consecutive biopsies: clinical correlation and insights into natural history and disease progression. Am J Surg Pathol 2007; 31: 1077–1088. · DOI
  40. Suefuji N, Niino D, Arakawa F, Karube K, Kimura Y, Kiyasu J et al. Clinicopathological analysis of a composite lymphoma containing both T- and B-cell lymphomas. Pathol Int 2012; 62: 690–698. · DOI
  41. Asmar F, Punj V, Christensen J, Pedersen MT, Pedersen A, Nielsen AB et al. Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma. Haematologica 2013; 98: 1912–1920. · DOI
  42. Zhao Z, Chen L, Dawlaty MM, Pan F, Weeks O, Zhou Y et al. Combined loss of Tet1 and Tet2 promotes B cell, but not myeloid malignancies, in mice. Cell Rep 2015; 13: 1692–1704. · DOI
  43. Arcaini L, Rossi D, Lucioni M, Nicola M, Bruscaggin A, Fiaccadori V et al. The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection. Haematologica 2015; 100: 246–252. · DOI
  44. Villamor N, Conde L, Martinez-Trillos A, Cazorla M, Navarro A, Bea S et al. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia 2013; 27: 1100–1106. · DOI
  45. Karube K, Martinez D, Royo C, Navarro A, Pinyol M, Cazorla M et al. Recurrent mutations of NOTCH genes in follicular lymphoma identify a distinctive subset of tumours. J Pathol 2014; 234: 423–430. · DOI

Cited by

Metadata

Authors
Nguyen, T. B., Sakata-Yanagimoto, M., Asabe, Y., Matsubara, D., Kano, J., Yoshida, K., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Izutsu, K., Nakamura, N., Takeuchi, K., Miyoshi, H., Ohshima, K., Minowa, T., Ogawa, S., Noguchi, M., & Chiba, S.
ORCID
Takeuchi, K
Venue
Blood Cancer Journal
Publisher
Springer Science and Business Media LLC
Published
2017-01-06
Volume
7
Issue
1
Pages
e516-e516
ISSN
2044-5385
DOI
10.1038/bcj.2016.122
PMC
PMC5301031
Cited by
93
References
7
Language
en
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